Retrovirus variation is an important component of retrovirus carcinogenesis and of the AIDS epidemic. Dr. Temin's group is using specially designed retrovirus vectors and helper cells to study the genetics of retroviruses and the rates an mechanisms of retrovirus variation. They have shown that base pair substitutions, frame-shifts, simple deletions, complex rearrangements, homologous recombination, and nonhomologous recombination occur at rates of 1 x 10-5, 7 x 10-7, 2 x 10- 6, 1 x 10-6, 4 x 10-5, and 4 x 10-8 per bp per cycle, respectively, for a simple C-type retrovirus. They propose further analysis of retrovirus mutation with different subfamilies of simple and complex retroviruses to determine whether these rates are the same or different and to determine what factors affect these rates. They will also further characterize retrovirus RNA dimerization, encapsidation, strand switching in reverse transcription, and recombination with simple retroviruses, and they will characterize recombination in complex retroviruses. These studies will give a more complete understanding of retrovirus genetics and the processes involved in retrovirus evolution.